RT Journal Article SR Electronic T1 Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site–Inhibited Factor VII JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 89 OP 95 DO 10.2967/jnumed.115.154849 VO 57 IS 1 A1 Nielsen, Carsten H. A1 Erlandsson, Maria A1 Jeppesen, Troels E. A1 Jensen, Mette M. A1 Kristensen, Lotte K. A1 Madsen, Jacob A1 Petersen, Lars C. A1 Kjaer, Andreas YR 2016 UL http://jnm.snmjournals.org/content/57/1/89.abstract AB Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an 18F-labeled derivative of factor VII. Methods: Active site–inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine–phenylalanine–arginine–chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-18F-fluorobenzoate and purified. The corresponding product, 18F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of 18F-FVIIai in the tumors measured in vivo by PET imaging. Results: The PET images showed high uptake of 18F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3–9.3 MBq of 18F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of 18F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of 18F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. Conclusion: 18F-FVIIai is a promising PET tracer for specific and noninvasive imaging of tumor TF expression. The tracer merits further development and clinical translation, with potential to become a companion diagnostics for emerging TF-targeted therapies.